Risk factors and treatment outcome of bloodstream infections caused by Pseudomonas aeruginosa isolates producing the PER-1 extended-spectrum b-lactamase

Abstract number: o75

Endimiani  A., Pini  B., Luzzaro  F., Amicosante  G., Rossolini  G.M., Toniolo  A.

Objectives: 

Clinical significance of bloodstream infection (BSI) due to Pseudomonas aeruginosa (Pa) has received large attention. In contrast, the clinical impact of BSI caused by ESBL-positive isolates has not been investigated. The PER-1 ESBL is a common enzyme conferring high-level resistance to anti-pseudomonal cephalosporins. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes caused by PER-1-positive Pa strains (PER-1-P-Pa).

Methods: 

From January 1998 to September 2004, 26 BSI cases due to ceftazidime-resistant Pa strains were observed at the Ospedale di Circolo, Varese, Italy. MIC values of anti-pseudomonal drugs were determined by the E-test method (AB Biodisk, Solna, Sweden). The double-disk synergy test was used to detect ESBL production. Molecular methods (PCR amplification and DNA sequencing) were used to characterize ESBL types. Clinical records of BSI-patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe-Jackson classification and Charlson weighted index), risk factors, antimicrobial therapy, and treatment outcome were investigated by comparing cases due to ESBL-positive to those due to ESBL-negative Pa isolates. Unpaired Student's t-test, Mann-Whitney U-test, and Chi-square were used for statistical analysis.

Results: 

Nine Pa isolates were found to express the PER-1 ESBL whereas the remaining 17 were PER-1-negative (PER-1-N-Pa). Severe sepsis (P = 0.03), bladder and intravascular catheters (both, P = 0.01), immunosuppressive therapy (P = 0.04), and mechanical ventilation (P = 0.03) were significantly associated with BSI due to PER-1-P-Pa. Empirical treatment (P = 0.02) and treatment after ID/AST (P < 0.01) were less adequate in PER-1-P-Pa cases. Hospital admission and longer mean length of hospital stay after BSI onset (P = 0.07 and P = 0.08, respectively) was possibly related to expression of the PER-1 enzyme. Overall, 77.8% BSI cases due to PER-1-P-Pa vs. 28.6% cases due to PER-1-N-Pa isolates failed to respond (P < 0.03). Notably, all cases due to PER-1-P-Pa that were treated with carbapenems failed to respond. In contrast, 7/8 cases due to PER-1-N-Pa given carbapenems were responders.

Conclusions: 

Therapeutic failure and poor outcome are associated with BSI episodes caused by PER-1-P-Pa strains. Thus, recognition and prompt reporting of ESBL-production appears a critical factor for the management of patients with serious P. aeruginosa infections.